A new phase III trial has shown that subcutaneous efgartigimod (Vyvgart Hytrulo) significantly improves symptoms in people with ocular myasthenia gravis, according to interim data presented at a recent neuromuscular medicine conference. The study, called ADAPT OCULUS, tested the drug’s efficacy in patients whose symptoms were limited to eye-related issues like double vision and drooping eyelids. Efgartigimod is a human immunoglobulin G1 (IgG1) antibody fragment that works by binding to the neonatal Fc receptor (FcRn), which reduces circulating IgG autoantibodies responsible for attacking nerve-muscle junctions.
Key Findings in Patient-Reported Outcomes
After four weeks of treatment, patients using efgartigimod saw an average improvement of 4.04 points on the Myasthenia Impairment Index (MGII) Patient-Reported Outcome (PRO) ocular score, compared to just 1.99 points for those given a placebo. The difference of 2.05 points was statistically significant, with a P-value of 0.012. This score measures symptoms like blurred vision, ptosis, and diplopia on a scale from 0 to 18, where higher numbers indicate worse disease severity. The MGII PRO scale is divided into two sections: a generalized score and an ocular score, with the ocular score specifically tracking eye-related symptoms, while the combined MGII PRO+PE score incorporates both patient-reported symptoms and physician examinations, ranging up to 23 total points.
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A secondary measure—combining patient-reported symptoms with physician examinations (MGII PRO+PE)—also showed meaningful improvement. The efgartigimod group improved by 5.02 points on average, versus 2.57 points for placebo, a difference of 2.44 points (P=0.018).
Jeff Guptill, a neurologist affiliated with the drug’s manufacturer and Duke University, emphasized that patient-reported symptoms are critical in assessing treatment effects. Retrospective analyses of efgartigimod studies in generalized myasthenia gravis have also indicated improvements in ocular symptoms, suggesting broader applicability of the treatment. The MGII PRO scale, which ranges from 0 to 23, was specifically designed to capture both physical and functional impacts, including the broader psychological and social burdens of the disease.
A Treatment Gap Filled
Ocular myasthenia gravis has historically received less research attention than the generalized form of the disease, leaving many patients without targeted therapies. Efgartigimod, originally approved in 2021 as an intravenous treatment for generalized myasthenia gravis, was later reformulated as a subcutaneous injection (efgartigimod PH20) in 2023. The ADAPT OCULUS trial included 141 patients with ocular myasthenia gravis, all of whom were on stable doses of acetylcholinesterase inhibitors, corticosteroids, or other immunosuppressive drugs. Participants had myasthenia gravis of any serotype, MGFA class I disease, and an MGII PRO ocular score of at least 6, ensuring they had measurable ocular symptoms at baseline.
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The 71 participants randomized to the efgartigimod group had a mean baseline age of 54 and 31% were women. Participants were randomly assigned to receive either 1,000 mg of efgartigimod weekly for four weeks or a placebo. Most trial participants (81.3%) had antibodies against acetylcholine receptors (AChR), while 16.9% were “triple seronegative”, meaning their blood tests did not detect antibodies against AChR, MuSK, or LRP4. Improvements in MGII PRO ocular scores were observed across both groups, suggesting the treatment may benefit patients regardless of antibody status.
Safety and Next Steps
Adverse events in the trial were consistent with previous studies of efgartigimod in generalized myasthenia gravis. The most common side effects included headache, redness at the injection site, and upper respiratory infections. There was one serious treatment-related adverse event in the initial phase and 17 total across both phases of the study. Currently, efgartigimod is not FDA-approved for ocular myasthenia gravis. However, the ADAPT OCULUS trial marks the first dedicated study of a targeted therapy for this specific condition, building on retrospective data from generalized myasthenia gravis trials that had hinted at ocular symptom improvements.
